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用于治疗骨科植入物感染的热敏性可注射双药负载壳聚糖基混合水凝胶。

Thermosensitive injectable dual drug-loaded chitosan-based hybrid hydrogel for treatment of orthopedic implant infections.

作者信息

Akhlaghi Neda, Najafpour-Darzi Ghasem

机构信息

Biotechnology Research Laboratory, Faculty of Chemical Engineering, Babol Noshirvani University of Technology, Shariati Avenue, Babol 47148-71167, Iran.

Biotechnology Research Laboratory, Faculty of Chemical Engineering, Babol Noshirvani University of Technology, Shariati Avenue, Babol 47148-71167, Iran.

出版信息

Carbohydr Polym. 2023 Nov 15;320:121138. doi: 10.1016/j.carbpol.2023.121138. Epub 2023 Jun 20.

DOI:10.1016/j.carbpol.2023.121138
PMID:37659783
Abstract

A myriad of therapeutic agents and drug delivery systems are available to the surgeons for treating orthopedic implant-associated infections (OIAI), but only very few have demonstrated their effectiveness in preventing bacteria colonization and biofilm formation due to challenges in the local and sustainable therapeutic release. To address this issue, in this work, a thermosensitive injectable hydrogel based on chitosan (CH)-integrated hydroxyapatite nanoparticles (HAP NPs) containing vancomycin (Van) and quercetin (QC)-loaded in F127 micelles (CH-HAP-FQ-Van hydrogel) was fabricated with potential application in the treatment of OIAI. This dual drug delivery system demonstrated a pH-sensitive drug release pattern. In addition, 100 % growth inhibition of Staphylococcus aureus for a duration of 14 days was observed. Apart from the strong antioxidant activities owing to the co-administration of QC even after 432 h, this composite hydrogel revealed 95.88 ± 2.8 % S. aureus biofilm eradication. By consideration of degradation stability (53.52 ± 4.24 %) during 60 days along with smart gelation within 10 min at 37 °C and easy injectability, CH-HAP-FQ-Van hydrogel could be used as a promising ideal local drug delivery system for implant-related infections.

摘要

外科医生有多种治疗药物和给药系统可用于治疗骨科植入物相关感染(OIAI),但由于局部和持续治疗释放方面的挑战,只有极少数药物在预防细菌定植和生物膜形成方面显示出有效性。为了解决这个问题,在这项工作中,制备了一种基于壳聚糖(CH)整合羟基磷灰石纳米颗粒(HAP NPs)的热敏注射水凝胶,其中含有负载在F127胶束中的万古霉素(Van)和槲皮素(QC)(CH-HAP-FQ-Van水凝胶),具有治疗OIAI的潜在应用价值。这种双药物递送系统表现出pH敏感的药物释放模式。此外,观察到对金黄色葡萄球菌的生长抑制率在14天内达到100%。除了由于QC共同给药即使在432小时后仍具有强大的抗氧化活性外,这种复合水凝胶还显示出95.88±2.8%的金黄色葡萄球菌生物膜根除率。考虑到60天内的降解稳定性(53.52±4.24%)以及在37°C下10分钟内的智能凝胶化和易于注射性,CH-HAP-FQ-Van水凝胶可作为一种有前途的理想局部药物递送系统用于植入物相关感染。

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